Localization of a novel susceptibility gene for familial ovarian cancer tochromosome 3p22-p25

We performed genome-wide linkage analysis in 58 patients and nine unaffecte d members among 28 families with no mutation in BRCA1 or BRCA2, employing a set of 410 microsatellite markers. We initially screened the whole genome, including the X chromosome, by a non-parametric method using the GENEHUNTE R program. As a result, chromosome 3p22-p25 showed a suggestive score for l inkage [LOD = 3.49 and non-parametric LOD (NPL)= 2.77 at D3S3611] based on a multipoint analysis. Additionally, based on a two-point analysis using de nse markers, this 3p22-p25 region showed a P-value < 0.05 at 10 markers and there is suggestive evidence for linkage at two markers within <similar to >19 cM (NPL = 2.60 and 2.49 at D3S1597 and D3S3611, respectively). To explo re whether the candidate gene in this 3p22-p25 region contributed to carcin ogenesis of familial ovarian cancer in a similar fashion to the tumor suppr essor gene, we performed loss of heterozygosity (LOH) analysis. It was obse rved that the frequency of LOH at four markers in this region was >50% only in tumor tissues from patients with no mutation in BRCA1 or BRCA2, not in those with a BRCA1 mutation.